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Examining the therapeutic efficacy of targeting FAO

 

By examining different novel therapies there can be a better understanding of the frontline strategy for clinical management. A research team lead by Zeyad Nassar examined the main bioenergetic pathway in prostate cancer which is fatty acid oxidation
(FAO). The main targeted therapies are antigen deprivation. Since the human prostate cancer (PCa) cells relies on androgens for growth and survival. FDA approved agents that more effectively targeted androgen signaling. The continuation of trials found the therapeutic strategy that enhance response to ADT which prevent or delay PCa progression.

The method involved looking into the key functional genes in PCs progression through a meta-analysis of 735 genes involved in lipid metabolism. In addition, a disease-relapse survival analysis was conducted using TCGA data for each top 20 genes. Through the metadata the researchers were able to find that DER1 mRNA expression was significantly higher in malignant compared to benign prostate tissue. It was also discovered that the top DECR1 increased copy gain was represented in hormone base cancers such as uterine, breast, and prostate.

DECR1 is an androgen-repressed gene in PCa which was shown in the mice models. Immunocytochemistry and Western blot of nuclear, cytoplasmic and mitochondrial cell fractions eas used to determine DECR1 linked to PCa progression and patient outcomes, and therefore might represent an unexplored therapeutic target. This repression of androgen divulged through the data that targeting DECR1 disrupts PUFA oxidation in PCa cells. In conclusion, the results showed targeting FAO oxidation is effective in patient PCa transfer. Also, Etomoxir effectively inhibited FAO tissues because of significant decrease in multiple acylcarnitines.

Author: Natasha Crumby

Reference:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7386908/